Our long-term goal is to understand the contribution of neural reward circuits to control of food intake during normal consumption as well as in pathologies that incorporate binge eating. We are specifically interested in how opioid signaling within reward circuits, particularly in the shell of the nucleus accumbens (sNAcc), mediates binge-like food intake. Stimulation of mu opioid receptors (MORs) in the sNAcc induces voracious feeding and sNAcc opioid receptor and ligand expression is altered in rat models of diet-induced binge eating. However, the mechanisms through which sNAcc MOR stimulation causes hyperphagia, and how diet-induced changes in this circuit contribute to binge eating behavior, remain poorly understood. In previous studies, we characterized two firing patterns in sNAcc neurons that we hypothesize play important and distinct roles in processing of taste hedonics and controlling appetitive food-seeking behavior. Our data suggests that the first of these firing patterns encodes palatability, while the second serves to permissively gate food-seeking behavior (and subsequent consumption) through a disinhibition mechanism. In the present proposal, we will test the hypothesis that distinct effects of sNAcc MOR stimulation on these firing patterns act to increase palatability-induced hyperphagia and food-seeking appetitive behaviors through signaling in segregated anatomical pathways. We further hypothesize that diet-induced binge eating arises specifically through sensitization of opioid signaling in the neural pathway mediating appetitive food-seeking, rather than through changes in pathways processing palatability. To address these hypotheses, we will use a combination of in vivo electrophysiological and pharmacological approaches to characterize the effects of sNAcc MOR manipulations on firing in efferent targets of the sNAcc. We will investigate interactions between the sNAcc and target regions using simultaneous electrode array recordings and cross-correlation techniques to characterize functional connectivity between these regions. Finally, we will characterize electrophysiological and pharmacological changes occurring in this circuit in a rat model of diet-induced binge eating. We anticipate that these experiments will provide important insights into the mechanisms underlying hyperphagia caused by sNAcc MOR stimulation and diet-induced binge eating. These experiments will lead to greater understanding of neural-circuit mechanisms underlying compulsive food intake, and are thus highly relevant in developing novel therapeutic interventions for eating disorders such as bulimia nervosa.